An Activity-Based Fluorescent Probe for Imaging Fluctuations of Peroxynitrite (ONOO-) in the Alzheimer's Disease Brain

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author Jong Seung Kim
journal Angewandte Chemie International Edition


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Peroxynitrite (ONOO-) plays a critical role in Alzheimer's disease (AD), and the association between ONOO- and AD is inexplicit. To reveal the ONOO- influxes in AD brains, an activatable activity-based fluorescence probe Rd-DPA3 was rationally designed by a structure-modulated strategy. Taking advantage of ONOO--sparked two-step cascade reactions of a novel chemical trigger, Rd-DPA3 specifically responds to ONOO- among 0.3 mM other ROS and varied proteins, accompanied by an intensive fluorescence enhancement (F/F0 = 50). Moreover, with the mitochondria-targeting ability, Rd-DPA3 can efficiently monitor the alternations of intracellular ONOO- levels in the cerebral cells during oxidative stress. Significantly, due to NIR emission and superb blood-brain barrier (BBB) crossing ability, Rd-DPA3 is capable of in vivo imaging cerebral ONOO- influxes and illustrating an age-dependent accumulation of native ONOO- in AD mice brains. This work discloses that Rd-DPA3 would be beneficial for AD diagnosis, treatment evaluation, and potential pathogenesis study.






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